Community-dwelling cocaine-dependent men and women respond differently to social stressors versus cocaine cues.

Medical University of South Carolina, 67 President St, Charleston, SC 29403, United States. angela.waldrop@ucsf.edu

Abstract

There are likely to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Cocaine-dependent women are more likely to attribute relapse to negative emotional states and interpersonal conflict. Cocaine dependence has also been linked to dysregulation of stress response and the hypothalamic pituitary adrenal (HPA) axis which may differ between genders. Subjective and HPA-axis responses to a social evaluative stressor, the Trier Social Stress Test (TRIER), and in vivo cocaine-related cues were examined in the present study.

RESULTS:

There were no gender differences in magnitude of craving responses to the TRIER or the CUE. Both genders had a greater craving response to the CUE than to the TRIER, but the magnitude of the difference was greater for men than women (p=0.04). Cocaine-dependent subjects, compared to the control group, had significantly higher response throughout the TRIER (p<0.0001) and CUE (p<0.0001) testing sessions. There were no gender differences and no gender by cocaine interaction for ACTH responses to the TRIER, although women had lower baseline ACTH (p=0.049). On the CUE task, in contrast, female cocaine-dependent subjects had a more blunted ACTH response than did the other three groups (p=0.02). Female cocaine-dependent subjects also had a lower odds of a positive cortisol response to the TRIER as compared to the other three groups (OR=0.84, 95% CI=[0.02, 1.01]). During the CUE task, cocaine-dependent subjects had overall higher mean cortisol levels (p=0.0001), and higher odds of demonstrating a positive cortisol response to the CUE (OR=2.61, 95% CI=[1.11, 6.11]). No gender differences were found in ACTH responses to the CUE. The results are reviewed in the context of the existing literature on gender differences in cocaine dependence and potential implications for treatment are discussed.

Subjective Reactivity to Trier Stress Task and Cocaine Cues in Cocaine-dependent Subjects: Peak Change from Baseline. A) While both genders had a greater craving response to the cues than the Trier (with women having greater overall craving response), the differential response to the tasks was greater in men than in women (p=0.04). B) The change in subjective stress response to the Trier was greater than the response to cocaine cues in all subjects (p=0.0002) and females reported a higher (though statistically insignificant) stress response to the Trier than did males.

Correlations between Subjective Stress and Craving. A significant correlation was found between peak stress and peak craving in both females (rS= 0.59, p=0.0019; A) and males (rS=0.39, p=0.04; B) in response to cocaine cues. During the Trier Stress Task, a significant correlation was found for females (rS=0.65, p=0.0015; C), but not males (rS=0.10, p=0.68; D).

ACTH Response to Cocaine Cues. Group means of ACTH levels over time indicate that female cocaine-dependent subjects had a more blunted HPA response to the cocaine cues than did the other three groups (p=0.02).

ACTH Response to Cocaine Cues: Male vs. Female. Cocaine- and control-groups were collapsed to show the different time courses of ACTH responses to cocaine cues; the interaction was significant even after controlling for baseline (p=0.01).

Cortisol Response to Trier Stress Task. Group means of cortisol levels over time demonstrate that cocaine-dependent females display blunted HPA response (OR=0.84, 95%CI=[0.02, 1.01]) to a social stressor as compared to cocaine-dependent males and healthy control subjects.

Cortisol Response to Cocaine Cues. Group means of cortisol levels over time indicate that cocaine-dependent subjects had higher cortisol levels than control subjects throughout the test (p=0.0001), as well as a higher likelihood of responding to the cocaine cues.